About this Research Topic
Allogeneic hematopoetic stem cell transplantation (HSCT) became standard of care for children with high-relapse-risk and relapsed acute lymphoblastic leukemia. Efficient conditioning regimen, availability of different donors, prevention of acute and chronic graft-versus host-disease and improved supportive care measures reduced severe acute toxicities over the last decade, but long-term side effects are a major concern. A recent prospective randomized trial has shown that pediatric patients who received myeloablative total body irradiation plus etoposide prior to HSCT had a significant better survival and lower relapse risk versus patients who received myeloablative chemotherapy. However, relapse is still the most common cause of treatment failure and needs additional strategies to solve this problem.
In the new era of immunotherapy, establishing options for high-risk patients for the best available salvage therapies will further improve long-term leukemia-free survival with less side effects. This includes reduction of minimal residual disease pre-transplant, substitution of toxic chemotherapy with bispecific antibodies, replacement of HSCT by CAR T-cell therapy, improved transplant strategies for specific groups, e.g. infants, adolescents and young adults and innovative treatments for acute and chronic GVHD. Furthermore, therapeutic drug monitoring and dose adjustment as well as contemporary radiation techniques might enable individualized therapies.
The goal of this manuscript collection is to discuss the most promising tools for preventing relapse of acute lymphoblastic leukemia. Risk-adapted pre-transplant strategies, novel transplantation modalities and monitoring of late effects are the topics for HSCT. On the other hand, we want to focus on innovative immunotherapies, e.g. CAR-T cells, bispecific antibodies, and compare their curative ability with transplant outcomes.
The specific thematic areas envisaged to be addressed in this article collection are the following:
• Are HLA-identical siblings still the best available donor for ALL?
• The challenge of treating “older children”: what is the best transplant strategy for ALL-AYAs?
• TKIs for Ph+ and Ph-like ALL: could we omit HSCT?
• Bispecific Antibodies before HSCT: less toxicity for better transplant outcome?
• CAR-T cell therapy:only bridge to transplant?
• T-cell depletion: PT-CY versus in vitro-TCD
• Why is TBI so effective in HR-ALL?
• TBI forever? New chemotherapeutic options for irradiation-free conditioning
• MRD: Which level of negativity is relevant?
• Current treatment options for acute GVHD in children
• Current treatment options for chronic GVHD in children
• Immunoreconstitution and chimerism: a different story compared to adults?
• Non-relapse mortality after HSCT: where are we now?
• High-risk ALL: Transplant indications in 2021
• Small molecules: double-feature prophylaxis against leukemia and GVHD?
• Transplantation for the youngest: better than chemotherapy?
The editors would welcome the contribution of Review, Methods, Hypothesis and Theory, Perspective, and Opinion articles.
Keywords: Lymphoblastic leukemia, allogeneic stem cell transplantation, CAR T-cells, Acute Lymphoblastic Leukemia, ALL
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